Background: Loneliness is widespread in adolescents and associated with a myriad of adverse physical and mental health outcomes. Exploring variables associated with loneliness is important for the development of targeted interventions. The aim of the current study was to explore associations between leisure-time sedentary behavior (LTSB) and loneliness in adolescents from 52 low- and middle-income countries. Methods: Data from the Global School-based Student Health Survey were analyzed. Data on past 12-month self-perceived loneliness and LTSB were collected. Multivariable logistic regression and meta-analysis were conducted to assess the associations. Results: Among 148,045 adolescents (mean age 13.7 +/- SD 1.0 years; 48.5% female), the prevalence of loneliness increased from 8.7% among those with 1-2 h/day of LTSB to 17.5% among those spending > 8 h/day sedentary. Compared to those who engage in less than 1 h of LTSB per day, the OR (95% CI) of loneliness for 1-2 h/day, 3-4 h/day, 5-8 h/day and > 8 h/day were 1.00 (0.91-1.11), 1.29 (1.15-1.45), 1.37 (1.17-1.61), and 1.66 (1.39-1.99), respectively. Limitations: The study is cross-sectional, therefore the directionality of the relationships cannot be deduced. Conclusions: Our data suggest that LTSB is associated with increased odds for feeling lonely in adolescence. Future longitudinal data are required to confirm/refute the findings to inform public health campaigns.